title: Structure and hemimethylated CpG binding of the SRA domain from human UHRF1.
abstract: Human UHRF1 (ubiquitin-like PHD and RING finger 1) functions to maintain CpG DNA methylation patterns through DNA replication by co-localizing with the DNA methyltransferase DNMT1 at chromatin in mammals. Recent studies show that UHRF1 binds selectively to hemimethylated CpG via its conserved SRA (SET- and RING finger-associated) domain. However, the underlying molecular mechanism is not known. Here, we report a 1.95 A resolution crystal structure of the SRA domain of human UHRF1. Using NMR structure-guided mutagenesis, electrophoretic mobility shift assay, and fluorescence anisotropy analysis, we determined key amino acid residues for methyl-DNA binding that are conserved in the SRA domain.
authors.affiliation: Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York University, New York, New York 10029, USA.
authors.forename: Chengmin
authors.initials: C
authors.lastname: Qian
authors.forename: Side
authors.initials: S
authors.lastname: Li
authors.forename: Jean
authors.initials: J
authors.lastname: Jakoncic
authors.forename: Lei
authors.initials: L
authors.lastname: Zeng
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Walsh
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhou
mesh_terms: D016880:Anisotropy; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D018899:CpG Islands; D018360:Crystallography, X-Ray / Q000379:methods; D004247:DNA / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D016296:Mutagenesis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence / Q000379:methods; D013696:Temperature; D044767:Ubiquitin-Protein Ligases
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004247:DNA; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases